Mammalian Inner Retinal Photoreception Robert J. Lucas  Current Biology  Volume 23, Issue 3, Pages R125-R133 (February 2013) DOI: 10.1016/j.cub.2012.12.029 Copyright © 2013 Elsevier Ltd Terms and Conditions

Figure 1 The discovery of intrinsically photosensitive retinal ganglion cells (ipRGCs). Two papers in 2002 reported the discovery of ipRGCs. Berson et al. [16] used retrograde tracing to identify the small number of ganglion cells (shown in red) that project to the SCN (site of the circadian clock) and using recording electrodes found that they are excited by light even when isolated from rod/cone input (Insert A shows depolarising responses from a SCN-projecting neurone when isolated from rod/cone influence and exposed to stimuli of increasing irradiance taken from that paper). Hattar et al. [17] showed that these back-labelled cells express melanopsin. Insert B left panel shows a single cell back-labelled from the SCN, filled with dye from a recording electrode (green) and counter stained for melanopsin (red). They also generated a reporter mouse in which melanopsin-expressing cells and axons could be stained blue, revealing that this photopigment is found in a subset of retinal ganglion cells. Insert B middle panel shows an en face view of the mouse retina, with blue-stained axons converging on the optic nerve head. This reporter also showed that the melanopsin-expressing ganglion cells strongly innervated the SCN. Insert B right-hand panel shows a ventral view of the mouse brain from a transgenic mouse. Note the strong blue stain in the optic nerves and in the hypothalamus above the optic chiasm. (Panels A and B were reproduced with permission from Science.) Current Biology 2013 23, R125-R133DOI: (10.1016/j.cub.2012.12.029) Copyright © 2013 Elsevier Ltd Terms and Conditions

Figure 2 The many functions of ipRGCs. The number of functions attributed to mammalian ipRGCs has grown progressively in the decade since their discovery. Through their central projection this small fraction of the total ganglion cell population (shown in red) entrain central circadian clocks; modulate the neuroendocrine and sleep/alertness systems; regulate pupil size; explain aspects of photophobia/photoallodynia, and light avoidance behaviours in rodents; and support brightness discrimination. There is also evidence that they influence cognitive function and may even contribute to visual pattern discrimination. Their impact on other aspects of vision remains little explored, but this could be extensive as ipRGCs not only set pupil size but also send signals within the retina that may entrain local circadian clocks and contribute to light adaptation in the retinal network. ipRGCs also influence the activity of many neurons in the thalamocortical projection. See text for further discussion and references. Current Biology 2013 23, R125-R133DOI: (10.1016/j.cub.2012.12.029) Copyright © 2013 Elsevier Ltd Terms and Conditions

Figure 3 Melanopsin and artificial lighting. Spectral power distributions for three different light sources: ‘480 nm’ (a near monochromatic light source predicted to be the most efficient for melanopsin), indoor lighting (natural + flourescent lighting in our office in Manchester), and ‘gloomy’ daylight (direct daylight in Manchester under low, thick cloud). Their divergence not only in total incident power, but also in its distribution across the spectrum highlights the challenge of quantification. Photopic illuminance (measured in ‘lux’) is calculated by weighting spectral power according to the photopic sensitivity function (V(λ)). However, melanopsin has quite different spectral sensitivity (approximated here by a ‘melanopic’ function (VZ(λ)) after [95]). As a result, if it were possible to increase the output of the indoor and 480 nm lighting such that they matched that of daylight when measured in lux, the effective photon flux for melanopsin would still be 60% lower for the indoor source, but 1000% higher for the 480 nm light. Current Biology 2013 23, R125-R133DOI: (10.1016/j.cub.2012.12.029) Copyright © 2013 Elsevier Ltd Terms and Conditions